Last reviewed · How we verify

NCT00759876

Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD)

Terminated Phase 2 Results posted Last updated 29 October 2020
What this trial tests

Phase 2 trial testing Ataluren in Duchenne Muscular Dystrophy in 36 participants. Terminated before completion.

Timeline
13 August 2008
Primary endpoint
17 May 2010
17 May 2010

Quick facts

Lead sponsorPTC Therapeutics
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment36
Start date13 August 2008
Primary completion17 May 2010
Estimated completion17 May 2010
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

PTC Therapeutics — full company profile →

Who can join

Eligibility, male only, with Duchenne Muscular Dystrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Primary · Baseline up to Week 89

TEAE: any untoward medical occurrence or undesirable event(s) that begins or worsens following administration of the study drug, whether or not considered related to the treatment by the Investigator. Severity of an adverse event (AE) was classified as: mild (does not interfere with usual function), moderate (interferes with usual function; may require medical intervention), severe (interferes significantly with usual function; likely require medical intervention), life-threatening, and fatal. Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a l

At least 1 TEAE
GroupValue95% CI
Ataluren36
Mild TEAE
GroupValue95% CI
Ataluren9
Moderate TEAE
GroupValue95% CI
Ataluren16
Severe TEAE
GroupValue95% CI
Ataluren10
Life-Threatening TEAE
GroupValue95% CI
Ataluren1
Fatal TEAE
GroupValue95% CI
Ataluren0
Related TEAE
GroupValue95% CI
Ataluren28
Serious TEAE
GroupValue95% CI
Ataluren6
Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT) Secondary · Baseline, Week 48 and Week 60

The 6MWD was assessed in participants who were ambulatory using standardized procedures. Participants were not permitted to use assistive devices during the 6MWD test. Only the results of the participant's best valid test at each visit were included in the analysis. The mean change from baseline in the distance the participant walked is reported.

Baseline
GroupValue95% CI
Ataluren367.8± 107.3
Change from Baseline at Week 48
GroupValue95% CI
Ataluren-80.4± 59.5
Change from Baseline at Week 60
GroupValue95% CI
Ataluren-101.5± 64.4
Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests Secondary · Baseline, Week 48 and Week 60

Timed function tests included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. Timed function tests were assessed in ambulatory participants. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used. Test results were set to missing in the analysis for participants who could not perform the tests for rea

Rise to Standing, Baseline
GroupValue95% CI
Ataluren13.57± 11.111
Rise to Standing, Change from Baseline at Week 48
GroupValue95% CI
Ataluren6.49± 8.059
Rise to Standing, Change from Baseline at Week 60
GroupValue95% CI
Ataluren5.77± 7.790
Walk/Run 10 m, Baseline
GroupValue95% CI
Ataluren7.62± 3.641
Walk/Run 10 m, Change from Baseline at Week 48
GroupValue95% CI
Ataluren3.15± 5.591
Walk/Run 10 m, Change from Baseline at Week 60
GroupValue95% CI
Ataluren3.20± 5.930
Ascend 4 Stairs, Baseline
GroupValue95% CI
Ataluren7.16± 7.481
Ascend 4 Stairs, Change from Baseline at Week 48
GroupValue95% CI
Ataluren4.92± 6.856
Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests Secondary · Baseline, Week 48 and Week 60

Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used for standing from supine position: 1) Unable to stand from supine, even with use of a chair. 2) Assisted Gowers, requires furniture to rise from supine to full upright posture. 3) Full Gowers, rolls over, stands with both hands "climbing up" legs to above knees to achieve full upright posture. 4) Half Gowers, rolls over, stands up with 1 hand support on lower legs. 5) Rolls to side and/or stands with 1 or both hands on floor to start to rise but does not touch legs. 6) St

Baseline
GroupValue95% CI
Ataluren3.25± 1.260
Change from Baseline at Week 48
GroupValue95% CI
Ataluren-0.58± 0.929
Change from Baseline at Week 60
GroupValue95% CI
Ataluren-0.62± 0.921
Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests Secondary · Baseline, Week 48 and Week 60

Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to run/walk 10-meters: 1) Unable to walk independently. 2) Unable to walk independently but can walk with knee-ankle-foot orthoses (KAFOs) or with support from a person 3) Highly adapted, wide-based lordotic gait, cannot increase walking speed. 4) Moderately adapted gait, can pick up speed but cannot run. 5) Able to pick up speed but runs with a double stance phase (that is, cannot achieve both feet off the ground). 6) Runs and gets both feet off the ground (with no doubl

Baseline
GroupValue95% CI
Ataluren4.42± 0.974
Change from Baseline at Week 48
GroupValue95% CI
Ataluren-0.25± 1.073
Change from Baseline at Week 60
GroupValue95% CI
Ataluren-0.57± 1.207
Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests Secondary · Baseline, Week 48 and Week 60

Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to ascend 4 stairs: 1) Unable to climb 4 standard stairs. 2) Climbs 4 standard stairs "marking time" (climbs 1 foot at a time, with both feet on a step before moving to next step), using both arms on 1 or both handrails. 3) Climbs 4 standard stairs "marking time" using 1 arm on 1 handrail. 4) Climbs 4 standard stairs "marking time" not needing handrail. 5) Climbs 4 standard stairs alternating feet, needs handrail for support. 6) Climbs 4 standard stairs alternating feet,

Baseline
GroupValue95% CI
Ataluren3.58± 1.717
Change from Baseline at Week 48
GroupValue95% CI
Ataluren-0.46± 1.141
Change from Baseline at Week 60
GroupValue95% CI
Ataluren-0.48± 1.365
Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests Secondary · Baseline, Week 48 and Week 60

Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to descend 4 stairs: 1) Unable to descend 4 standard stairs. 2) Descends 4 standard stairs "marking time" (climbs 1 foot at a time, with both feet on a step before moving to next step), using both arms on 1 or both handrails. 3) Descends 4 standard stairs "marking time", using 1 arm on 1 handrail. 4) Descends 4 standard stairs "marking time", not needing handrail. 5) Descends 4 standard stairs alternating feet in both directions, needs handrail for support. 6) Descends 4

Baseline
GroupValue95% CI
Ataluren3.63± 1.740
Change from Baseline at Week 48
GroupValue95% CI
Ataluren-0.04± 1.160
Change from Baseline at Week 60
GroupValue95% CI
Ataluren-0.10± 0.889
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry Secondary · Baseline, Week (Wk) 48 and Wk 60

Upper extremity myometry was performed using a hand-held dynamometer following standardized procedures. With this system, evaluators judged the strength of each muscle using an 11-point descriptive scoring system. From the individual muscle-group scores, a total composite score was derived. Bilateral assessments were done, and 3 measurements were recorded from each muscle group on each side, when possible. The best of the 3 replicates was used in the analysis. An increase from Baseline is reflective of increased muscle strength, whereas a decrease from Baseline is reflective of decreased muscl

Left (L) Knee Flexion, Baseline
GroupValue95% CI
Ataluren9.48± 4.395
L Knee Flexion, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren1.23± 2.715
L Knee Flexion, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren0.64± 3.079
Right (R) Knee Flexion, Baseline
GroupValue95% CI
Ataluren10.15± 5.439
R Knee Flexion, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren0.81± 2.254
R Knee Flexion, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren-0.05± 2.240
L Knee Extension, Baseline
GroupValue95% CI
Ataluren8.63± 5.124
L Knee Extension, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren-1.07± 1.842
Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 Secondary · Baseline, Week 48 and Week 60

Heart rate was measured with a Polar RS400 heart rate monitor, which consists of a transmitter strap worn around the chest and a wristwatch receiver. The monitor produces a digital text file with 1 value per minute that represents the mean heart rate for that minute. Mean heart rate values were collected before, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position before the 6MWT, and the mean heart rate for the last minute of this rest period was obtained and documented as the resting heart rate. During the 6MWT, the mean heart rate was collected and document

Resting Heart Rate, Baseline
GroupValue95% CI
Ataluren106.46± 11.163
Resting Heart Rate, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren8.30± 12.382
Resting Heart Rate, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren5.16± 11.197
Active Heart Rate, Baseline
GroupValue95% CI
Ataluren152.17± 13.457
Active Heart Rate, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren3.86± 12.365
Active Heart Rate, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren-2.84± 17.238
Recovery Heart Rate, Baseline
GroupValue95% CI
Ataluren113.13± 12.664
Recovery Heart Rate, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren4.64± 9.079
Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task Secondary · Baseline, Week 48 and Week 60

The digit span task is a 2-part (forward and backward) test in which a series of digits (3 to 9) were presented to participant in an auditory format only. For forward condition, the participant was to repeat digits back in the order they were presented. For backward condition, the participant was to reverse the order of presentation. Maximum score for each part (digit forward and digit backward) of task is 14; participants received a score of 2 points if they passed both trials, score of 1 point if they passed only 1 trial, and score of 0 points if they failed both trials. A raw score of total

Recalled Forward, Baseline
GroupValue95% CI
Ataluren3.66± 2.378
Recalled Forward, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren0.14± 1.353
Recalled Forward, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren0.04± 1.453
Recalled Backward, Baseline
GroupValue95% CI
Ataluren3.15± 2.524
Recalled Backward, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren0.74± 1.442
Recalled Backward, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren0.74± 1.442
Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory Secondary · Baseline, Week 48 and Week 60

The PedsQL Generic Core Scales comprises 23 questions, which are grouped into 4 scales (physical functioning, emotional functioning, social functioning, and school functioning); the fatigue-specific module included an additional 18 questions. The appropriate age-specific version was completed. On PedsQL Generic Core Scales, items were reversed scored and linearly transformed to a 0 to 100 scale so that higher scores indicate a better HRQL (0=100, 1=75, 2=50, 3=25, and 4=0). Mean is the sum of the items over the number of items that were answered (which accounts for missing data) to create scal

Physical Functioning, Baseline
GroupValue95% CI
Ataluren45.13± 21.114
Physical Functioning Change from Baseline at Wk 48
GroupValue95% CI
Ataluren3.16± 20.180
Physical Functioning Change from Baseline at Wk 60
GroupValue95% CI
Ataluren6.25± 23.545
Emotional Functioning, Baseline
GroupValue95% CI
Ataluren65.29± 16.141
Emotional Function, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren8.24± 18.294
Emotional Function, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren12.22± 17.614
Social Functioning, Baseline
GroupValue95% CI
Ataluren61.80± 16.914
Social Functioning, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren4.82± 19.463
Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory Secondary · Baseline, Week 48 and Week 60

The PedsQL Generic Core Scales comprises 23 questions, which are grouped into 4 scales (physical functioning, emotional functioning, social functioning, and school functioning); the fatigue-specific module included an additional 18 questions. The appropriate age-specific version was completed. On PedsQL Generic Core Scales, items were reversed scored and linearly transformed to a 0 to 100 scale so that higher scores indicate a better HRQL (0=100, 1=75, 2=50, 3=25, and 4=0). Mean is the sum of the items over the number of items that were answered (which accounts for missing data) to create scal

Physical Functioning, Baseline
GroupValue95% CI
Ataluren48.07± 21.111
Physical Functioning Change from Baseline at Wk 48
GroupValue95% CI
Ataluren2.31± 20.284
Physical Functioning Change from Baseline at Wk 60
GroupValue95% CI
Ataluren1.85± 19.366
Emotional Functioning, Baseline
GroupValue95% CI
Ataluren69.45± 17.465
Emotional Function, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren5.27± 19.595
Emotional Function, Change from Baseline at Wk 60
GroupValue95% CI
Ataluren3.29± 20.021
Social Functioning, Baseline
GroupValue95% CI
Ataluren57.95± 19.397
Social Functioning, Change from Baseline at Wk 48
GroupValue95% CI
Ataluren9.38± 16.956

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 89. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ataluren
Serious: 6/36 (17%)
Deaths:

Serious adverse events (6 terms)

ReactionSystemAtaluren
HypertensionVascular disorders
InfluenzaInfections and infestations
PneumoniaInfections and infestations
Femur fractureInjury, poisoning and procedural complications
Muscle contractureMusculoskeletal and connective tissue disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (70 terms — click to expand)

ReactionSystemAtaluren
VomitingGastrointestinal disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
FlatulenceGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
FallInjury, poisoning and procedural complications
Nasal congestionRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
Postprocedural discomfortInjury, poisoning and procedural complications
Muscular weaknessMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
ContusionInjury, poisoning and procedural complications
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
InfluenzaInfections and infestations
Joint injuryInjury, poisoning and procedural complications
Joint sprainInjury, poisoning and procedural complications
Weight decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Joint contractureMusculoskeletal and connective tissue disorders
ScoliosisMusculoskeletal and connective tissue disorders
Sinus congestionRespiratory, thoracic and mediastinal disorders
Disease progressionGeneral disorders
Gait disturbanceGeneral disorders
BronchitisInfections and infestations
RhinitisInfections and infestations
Procedural painInjury, poisoning and procedural complications
MyalgiaMusculoskeletal and connective tissue disorders
MigraineNervous system disorders
Respiratory tract congestionRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Stomach discomfortGastrointestinal disorders
AstheniaGeneral disorders
NasopharyngitisInfections and infestations
ExcoriationInjury, poisoning and procedural complications

Most-reported serious reactions: Hypertension, Influenza, Pneumonia, Femur fracture, Muscle contracture, Respiratory failure.

Data from ClinicalTrials.gov NCT00759876 adverse events section.

Sponsor's own description

Duchenne muscular dystrophy (DMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of DMD in approximately 10-15% of boys with the disease. Ataluren is an orally-delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a extension trial that will evaluate the long-term safety of ataluren in boys with nonsense mutation DMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, strength, and other important clinical and laboratory measures.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Assessment and management of respiratory function in patients with Duchenne muscular dystrophy: current and emerging options.
    LoMauro A, D'Angelo MG, Aliverti A. · · 2015 · cited 67× · PMID 26451113 · DOI 10.2147/tcrm.s55889
  2. Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients.
    McDonald CM, Muntoni F, Penematsa V, Jiang J, et al · · 2022 · cited 45× · PMID 34791888 · DOI 10.2217/cer-2021-0196
  3. Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.
    Szwec S, Kapłucha Z, Chamberlain JS, Konieczny P. · · 2024 · cited 14× · PMID 37917377 · DOI 10.1007/s40259-023-00632-3
  4. Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases.
    Chiu W, Hsun YH, Chang KJ, Yarmishyn AA, et al · · 2020 · cited 10× · PMID 33339321 · DOI 10.3390/ijms21249589
  5. Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents.
    Wilton SD, Fletcher S. · · 2011 · cited 1× · PMID 23776365 · DOI 10.2147/tacg.s8762

Verify or expand the search:

Other trials of Ataluren

Trials testing the same drug.

Other recruiting trials for Duchenne Muscular Dystrophy

Currently open trials in the same condition.

Other PTC Therapeutics trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00759876.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing